Establishing the cost of Xpert MTB/RIF mobile testing in high-burden peri-mining communities in South Africa.

BACKGROUND: Globally, tuberculosis remains a major cause of mortality, with an estimated 1.3 million deaths per annum. The Xpert MTB/RIF assay is used as the initial diagnostic test in the tuberculosis diagnostic algorithm. To extend the national tuberculosis testing programme in South Africa, mobile units fitted with the GeneXpert equipment were introduced to high-burden peri-mining communities. OBJECTIVE: This study sought to assess the cost of mobile testing compared to traditional laboratory-based testing in a peri-mining community setting. METHODS: Actual cost data for mobile and laboratory-based Xpert MTB/RIF testing from 2018 were analysed using a bottom-up ingredients-based approach to establish the annual equivalent cost and the cost per result. Historical cost data were obtained from supplier quotations and the local enterprise resource planning system. Costs were obtained in rand and reported in United States dollars (USD). RESULTS: The mobile units performed 4866 tests with an overall cost per result of $49.16. Staffing accounted for 30.7% of this cost, while reagents and laboratory equipment accounted for 20.7% and 20.8%. The cost per result of traditional laboratory-based testing was $15.44 US dollars (USD). The cost for identifying a tuberculosis-positive result using mobile testing was $439.58 USD per case, compared to $164.95 USD with laboratory-based testing. CONCLUSION: Mobile testing is substantially more expensive than traditional laboratory services but offers benefits for rapid tuberculosis case detection and same-day antiretroviral therapy initiation. Mobile tuberculosis testing should however be reserved for high-burden communities with limited access to laboratory testing where immediate intervention can benefit patient outcomes.

Scaling up Xpert MTB/RIF technology: the costs of laboratory- vs. clinic-based roll-out in South Africa.

OBJECTIVE: The World Health Organization recommends using Xpert MTB/RIF for diagnosis of pulmonary tuberculosis (PTB), but there is little evidence on the optimal placement of Xpert instruments in public health systems. We used recent South African data to compare the cost of placing Xpert at points of TB treatment (all primary clinics and hospitals) with the cost of placement at sub-district laboratories. METHODS: We estimated Xpert's cost/test in a primary clinic pilot and in the pilot phase of the national Xpert roll-out to smear microscopy laboratories; the expected future volumes for each of 223 laboratories or 3799 points of treatment; the number and cost of Xpert instruments required and the national cost of using Xpert for PTB diagnosis for each placement scenario in 2014. RESULTS: In 2014, South Africa will test 2.6 million TB suspects. Laboratory placement requires 274 Xpert instruments, while point-of-treatment placement requires 4020 instruments. With an Xpert cartridge price of $14.00, the cost/test is $26.54 for laboratory placement and $38.91 for point-of-treatment placement. Low test volumes and a high number of sites are the major contributors to higher point-of-treatment costs. National placement of Xpert at laboratories would cost $71 million/year; point-of-treatment placement would cost $107 million/year, 51% more. CONCLUSION: Placing Xpert technology at points of treatment is substantially more expensive than placing the instruments in smear microscopy laboratories. The incremental benefits of point-of-treatment placement, in terms of better patient outcomes, will have to be equally substantial to justify the additional cost to the national health budget.

Cost-effectiveness of laboratory monitoring for management of HIV treatment in sub-Saharan Africa: a model-based analysis.

OBJECTIVE: To compare the cost-effectiveness of three different strategies for long-term monitoring of antiretroviral therapy (ART) failure and regimen switching in sub-Saharan Africa: a symptom-based approach, or monitoring of either CD4 cell counts or plasma viral load (pVL). DESIGN: Markov model. SETTING AND PARTICIPANTS: Hypothetical HIV-infected adult population who began first-line ART and subsequently had up to 6 years of follow-up. MAIN OUTCOME MEASURES: Total cost, life expectancy and incremental cost-effectiveness ratio (ICER). RESULTS: A symptom-based approach yielded a life expectancy of 64.0 months at a total cost of US$ 4028 per person. All laboratory-based strategies, at testing intervals of 6 or 12 months, were cost-saving and improved life expectancy, compared with a symptom-based approach. The life-expectancy gain was larger for pVL than for CD4 strategies at 6-monthly (2.3 and 0.9 months, respectively) and 12-monthly testing (2.0 and 0.8 months, respectively). Cost-savings of 6-monthly pVL or CD4 testing were similar (US$ 630 and 621, respectively), whereas 12-monthly CD4 cell counts were more cost-saving than 12-monthly pVL (US$ 1132 and 880, respectively). Testing every 12 months - rather than every 6 months - decreased the ICER by 102% for CD4 cell count and 67% for pVL. These findings were robust to a wide range of deterministic sensitivity analyses, but were sensitive to the specificity and costs of diagnostic tests. CONCLUSION: Additional diagnostic costs are balanced by cost-savings from avoiding unnecessary switching due to misdiagnosis of ART failure. Routine pVL monitoring may be preferred as a replacement for CD4 cell counts because of its additional public-health advantages in preventing drug-resistance, supporting adherence and reducing HIV transmission.

Building capacity for the assessment of HIV drug resistance: experiences from the PharmAccess African Studies to Evaluate Resistance network.

The PharmAccess African Studies to Evaluate Resistance (PASER) network was established as a collaborative partnership of clinical sites, laboratories, and research groups in 6 African countries; its purpose is to build research and laboratory capacity in support of a coordinated effort to assess population-level acquired and transmitted human immunodeficiency virus type-1 drug resistance (HIVDR), thus contributing to the goals of the World Health Organization Global HIV Drug Resistance Network. PASER disseminates information to medical professionals and policy makers and conducts observational research related to HIVDR. The sustainability of the network is challenged by funding limitations, constraints in human resources, a vulnerable general health infrastructure, and high cost and complexity of molecular diagnostic testing. This report highlights experiences and challenges in the PASER network from 2006 to 2010.

Clinical research and development of tuberculosis diagnostics: moving from silos to synergy.

The development, evaluation, and implementation of new and improved diagnostics have been identified as critical needs by human immunodeficiency virus (HIV) and tuberculosis researchers and clinicians alike. These needs exist in international and domestic settings and in adult and pediatric populations. Experts in tuberculosis and HIV care, researchers, healthcare providers, public health experts, and industry representatives, as well as representatives of pertinent US federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health, United States Agency for International Development) assembled at a workshop proposed by the Diagnostics Working Group of the Federal Tuberculosis Taskforce to review the state of tuberculosis diagnostics development in adult and pediatric populations.

The net cost of incorporating resistance testing into HIV/AIDS treatment in South Africa: a Markov model with primary data.

BACKGROUND: Current guidelines for providing antiretroviral therapy (ART) in South Africa's public sector programme call for switching patients from first-line to second-line treatment upon virologic failure as indicated by two consecutive viral loads above 5000 copies/ml, but without laboratory evidence of viral resistance. We modelled the net cost of adding resistance testing for patients with virological failure and retaining patients without resistance on first-line therapy, rather than switching all failures to second-line therapy. METHODS: Costs were estimated for three scenarios: routine maintenance (standard care without resistance testing, switch all failures to second line); resistance testing (resistance test for patients with failure, switch those with resistance); and limited testing (resistance test for patients with failure in the first three years, switch those with resistance). A Markov model was used to estimate the cost of each arm over five years after first line initiation. Rates of treatment failure, viral resistance and treatment costs were estimated with primary data from a large HIV treatment cohort at a public facility in Johannesburg. Future costs were discounted at 3%. RESULTS: Virological failure rates over five years were 19.8% in routine maintenance and 20.2% in resistance testing and limited testing; 16.8% and 11.4% of failures in routine and limited testing, respectively, did not have any resistance mutations, resulting in 3.1% and 2.0% fewer patients switching to second-line ART by the end of five years. Treatment costs were estimated at US$526 and $1268 per patient per year on first-line and second-line therapy, respectively; a resistance test cost $242. The total average cost per patient over five years was $2780 in routine maintenance; $2775 in resistance testing; and $2763 in limited testing. CONCLUSIONS: Incorporating resistance testing into treatment guidelines in South Africa is potentially cost-neutral and can identify other reasons for failure, conserve treatment options, and generate information about emerging resistance patterns.

African regional external quality assessment for CD4 T-cell enumeration: development, outcomes, and performance of laboratories.

BACKGROUND: An independent African Regional External Quality Assessment Scheme (AFREQAS) was implemented from Johannesburg. The aim was to establish a network of CD4 laboratories supporting HIV/AIDS anti-retroviral therapy programs and improve the quality of regional CD4 testing with EQA assessment, feedback, remedial action, and technical training. The overall performance from 2002 to 2006 (Trials 1-20) is reported, together with cumulative longitudinal performance of the different CD4 methods used. METHODS: Stabilized blood samples with "normal" and/or "low" CD4 values were shipped over 20 Trials. Data was analyzed for each trial including trimmed mean, standard deviation, and percentage coefficient of variation (%CV); "Residual" and SDI values were also calculated for each participating laboratory for both absolute CD4 counts (CD4abs) and CD4 percentage of lymphocytes values (CD4%/Ly). Standardized individual laboratory SDI values across 20 trials were analyzed according to CD4 method. RESULTS: Average participation was 91.5%. Overall AFREQAS between-laboratory reproducibility (trimmed %CV) was 10.5% and 9.1% for absolute CD4 and CD4%/Ly, respectively. For the respective CD4abs and CD4%/Ly values in the trials where "normal" material was shipped trimmed %CV of 10.9 and 7.3% were noted, and in "low" value shipments %CV of 13.8% and 12.4% were noted. Cumulative absolute CD4 SDI analysis revealed the best between-laboratory precision amongst FACSCount and PanLeucogating (PLG-CD4) users (both SD of SDI = <1.2 and %CV of <<8%). Dual Platform or Single Platform algorithm-based systems and certain volumetric methods (laboratories who used Partec CyFlow instruments) had higher numbers of outlying laboratories (>12-25%CV and SD(SDI) > 2.2 noted), indicating that additional technical training and/or manufacturer support was required. CONCLUSIONS: Participation in an AFREQAS with feedback and remedial action improves the quality of CD4 testing. African laboratory professionals can easily master CD4 counting technologies. However, the introduction of the simplest and most cost-effective methodologies is required to take ownership, and enable the delivery of quality CD4 counts in vast numbers necessary to support expansion of African ART programs.

Dried blood spots improve access to HIV diagnosis and care for infants in low-resource settings.

Effective health care delivery to the majority of perinatally exposed infants worldwide, including those enrolled in prevention of mother-to-child transmission programs, is hampered by lack of access to an HIV diagnosis in infancy. Dried blood spot collection from young infants for centralized HIV polymerase chain reaction (PCR) testing is attainable in low-resource settings, provided PCR methodology suitable for routine laboratory service is available. The accuracy of the Roche Amplicor HIV-1 DNA test version 1.5 (Branchburg, NJ) performed on dried blood spots collected prospectively on ordinary Whatman filter paper from a cohort of 300 6-week-old infants born to HIV-infected women in Johannesburg, South Africa, was assessed. Anonymous analysis of the blood spots using a unique DNA extraction procedure was performed in a routine diagnostic laboratory and the results compared with HIV DNA and RNA PCR liquid blood tests at age 6 weeks, and the HIV status of the infant. Dried blood spots were available for 288 infants (96%) of whom 25 (8.7%) were HIV infected. The Roche Amplicor assay yielded a sensitivity of 100% and a specificity of 99.6%. HIV DNA PCR tests on dried blood spots have the potential to improve health care delivery to HIV-affected children in low-resource settings right now.

Affordable diagnosis of human immunodeficiency virus infection in infants by p24 antigen detection.

The expense of PCR testing limits diagnosis of HIV infection in infancy in low resource settings. The ultrasensitive p24 antigen assay has been proposed as an accurate substitute; however, its ability to detect different HIV viral subtypes remains to be determined. A sensitivity of 98.1% and specificity of 98.7% was obtained testing 203 samples from 24 HIV-infected and 66 uninfected infants born to HIV subtype C-infected women.